Project Details
Projekt
Patched-dependent regulation of intracellular endocannabinoid trafficking and its function in signalling and metabolism (19)
Subject Area
Cell Biology
Term
from 2014 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 112927078
The Hedgehog signaling pathway has conserved functions in regulating tissue growth, differentiation and homeostasis. The pathway has both transcriptional and metabolic outputs that appear to be separately controlled, but the mechanisms that distinguish them are unclear. We’ve shown that endocannabinoids repress the transcriptional output of the Hh pathway by binding to and destabilizing the 7 pass TM protein Smoothened (Smo). The Hh receptor Patched regulates Smo activity by controlling the intracellular trafficking of these lipid signaling molecules. Independent of its effects on Smo, Patched also modulates trafficking of endocnanabinoids to mitochondria. This proposal aims to 1) uncover the intracellular trafficking pathways through which endocannabinoids access Smo 2) identify the molecular machinery that promotes endocannabinoid mobilization to mitochondria and 3) determine how the presence of endocannabinoids in mitochondria influence their activity.
DFG Programme
CRC/Transregios
Applicant Institution
Ruprecht-Karls-Universität Heidelberg
Project Heads
Professorin Dr. Suzanne Eaton, until 7/2019 (†); Dr. André Georg Nadler, since 7/2020; Professor Marino Zerial, Ph.D., since 7/2020
